581 research outputs found
Site-specific characterisation of SARS-CoV-2 spike glycoprotein receptor binding domain
The novel coronavirus SARS-CoV-2, the infective agent causing COVID-19, is having a global impact both in terms of human disease as well as socially and economically. Its heavily glycosylated spike glycoprotein is fundamental for the infection process, via its receptor binding domains interaction with the glycoprotein angiotensin converting enzyme 2 on human cell surfaces. We therefore utilized an integrated glycomic and glycoproteomic analytical strategy to characterise both N- and O- glycan site specific glycosylation within the receptor binding domain. We demonstrate the presence of complex type N-glycans with unusual fucosylated LacdiNAc at both sites N331 and N343 and a single site of O-glycosylation on T323
Improving gait classification in horses by using inertial measurement unit (IMU) generated data and machine learning
For centuries humans have been fascinated by the natural beauty of horses in motion and their different gaits. Gait classification (GC) is commonly performed through visual assessment and reliable, automated methods for real-time objective GC in horses are warranted. In this study, we used a full body network of wireless, high sampling-rate sensors combined with machine learning to fully automatically classify gait. Using data from 120 horses of four different domestic breeds, equipped with seven motion sensors, we included 7576 strides from eight different gaits. GC was trained using several machine-learning approaches, both from feature-extracted data and from raw sensor data. Our best GC model achieved 97% accuracy. Our technique facilitated accurate, GC that enables in-depth biomechanical studies and allows for highly accurate phenotyping of gait for genetic research and breeding. Our approach lends itself for potential use in other quadrupedal species without the need for developing gait/animal specific algorithms
Testing foundations of quantum mechanics with photons
The foundational ideas of quantum mechanics continue to give rise to
counterintuitive theories and physical effects that are in conflict with a
classical description of Nature. Experiments with light at the single photon
level have historically been at the forefront of tests of fundamental quantum
theory and new developments in photonics engineering continue to enable new
experiments. Here we review recent photonic experiments to test two
foundational themes in quantum mechanics: wave-particle duality, central to
recent complementarity and delayed-choice experiments; and Bell nonlocality
where recent theoretical and technological advances have allowed all
controversial loopholes to be separately addressed in different photonics
experiments.Comment: 10 pages, 5 figures, published as a Nature Physics Insight review
articl
Primary and malignant cholangiocytes undergo CD40 mediated Fas dependent Apoptosis, but are insensitive to direct activation with exogenous fas ligand
Introduction
Cholangiocarcinoma is a rare malignancy of the biliary tract, the incidence of which is rising, but the pathogenesis of which remains uncertain. No common genetic defects have been described but it is accepted that chronic inflammation is an important contributing factor. We have shown that primary human cholangiocyte and hepatocyte survival is tightly regulated via co-operative interactions between two tumour necrosis family (TNF) receptor family members; CD40 and Fas (CD95). Functional deficiency of CD154, the ligand for CD40, leads to a failure of clearance of biliary tract infections and a predisposition to cholangiocarcinoma implying a direct link between TNF receptor-mediated apoptosis and the development of cholangiocarcinoma.
Aims
To determine whether malignant cholangiocytes display defects in CD40 mediated apoptosis. By comparing CD40 and Fas-mediated apoptosis and intracellular signalling in primary human cholangiocytes and three cholangiocyte cell lines.
Results
Primary cholangiocytes and cholangiocyte cell lines were relatively insensitive to direct Fas-mediated killing with exogenous FasL when compared with Jurkat cells, which readily underwent Fas-mediated apoptosis, but were extremely sensitive to CD154 stimulation. The sensitivity of cells to CD40 activation was similar in magnitude in both primary and malignant cells and was STAT-3 and AP-1 dependent in both.
Conclusions
1) Both primary and malignant cholangiocytes are relatively resistant to Fas–mediated killing but show exquisite sensitivity to CD154, suggesting that the CD40 pathway is intact and fully functional in both primary and malignant cholangiocytes 2) The relative insensitivity of cholangiocytes to Fas activation demonstrates the importance of CD40 augmentation of Fas dependent death in these cells. Agonistic therapies which target CD40 and associated intracellular signalling pathways may be effective in promoting apoptosis of malignant cholangiocytes
Quantum walks: a comprehensive review
Quantum walks, the quantum mechanical counterpart of classical random walks,
is an advanced tool for building quantum algorithms that has been recently
shown to constitute a universal model of quantum computation. Quantum walks is
now a solid field of research of quantum computation full of exciting open
problems for physicists, computer scientists, mathematicians and engineers.
In this paper we review theoretical advances on the foundations of both
discrete- and continuous-time quantum walks, together with the role that
randomness plays in quantum walks, the connections between the mathematical
models of coined discrete quantum walks and continuous quantum walks, the
quantumness of quantum walks, a summary of papers published on discrete quantum
walks and entanglement as well as a succinct review of experimental proposals
and realizations of discrete-time quantum walks. Furthermore, we have reviewed
several algorithms based on both discrete- and continuous-time quantum walks as
well as a most important result: the computational universality of both
continuous- and discrete- time quantum walks.Comment: Paper accepted for publication in Quantum Information Processing
Journa
Can One Trust Quantum Simulators?
Various fundamental phenomena of strongly-correlated quantum systems such as
high- superconductivity, the fractional quantum-Hall effect, and quark
confinement are still awaiting a universally accepted explanation. The main
obstacle is the computational complexity of solving even the most simplified
theoretical models that are designed to capture the relevant quantum
correlations of the many-body system of interest. In his seminal 1982 paper
[Int. J. Theor. Phys. 21, 467], Richard Feynman suggested that such models
might be solved by "simulation" with a new type of computer whose constituent
parts are effectively governed by a desired quantum many-body dynamics.
Measurements on this engineered machine, now known as a "quantum simulator,"
would reveal some unknown or difficult to compute properties of a model of
interest. We argue that a useful quantum simulator must satisfy four
conditions: relevance, controllability, reliability, and efficiency. We review
the current state of the art of digital and analog quantum simulators. Whereas
so far the majority of the focus, both theoretically and experimentally, has
been on controllability of relevant models, we emphasize here the need for a
careful analysis of reliability and efficiency in the presence of
imperfections. We discuss how disorder and noise can impact these conditions,
and illustrate our concerns with novel numerical simulations of a paradigmatic
example: a disordered quantum spin chain governed by the Ising model in a
transverse magnetic field. We find that disorder can decrease the reliability
of an analog quantum simulator of this model, although large errors in local
observables are introduced only for strong levels of disorder. We conclude that
the answer to the question "Can we trust quantum simulators?" is... to some
extent.Comment: 20 pages. Minor changes with respect to version 2 (some additional
explanations, added references...
Exploring Options for Enhancement of Social Dialogue Between the Turkish and Greek Communities in Cyprus Using the Structured Dialogic Design Process
Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin
One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution
Frequency-resolved Monte Carlo
We adapt the Quantum Monte Carlo method to the cascaded formalism of quantum optics, allowing us to simulate the emission of photons of known energy. Statistical processing of the photon clicks thus collected agrees with the theory of frequency-resolved photon correlations, extending the range of applications based on correlations of photons of prescribed energy, in particular those of a photon-counting character. We apply the technique to autocorrelations of photon streams from a two-level system under coherent and incoherent pumping, including the Mollow triplet regime where we demonstrate the direct manifestation of leapfrog processes in producing an increased rate of two-photon emission events
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